The marine tube sponge Cribrochaline olemda produces the kapakahines A-G, which are a class of novel cyclic peptides that contain both unique gross structure and an unusual peptide linkage. Recent preliminary biological studies (mouse model) conducted by Yoichi Nakao and co-workers at the University of Tokyo, Japan, have uncovered some promising anti-malarial activity by the kapakahine alkaloids. In order to further investigate this promising biological data (i.e. monkey model), larger sample amounts will be needed, which cannot be attained from the natural source. Because of their limited availability from the host organism, laboratory synthesis will be required for additional biological experimentation. The first goal of this research program is the development and application of an asymmetric intramolecular Heck cyclization to construct the chiral tertiary-carbinyl heterocyclic amine. This is the defining feature of these marine alkaloids for which no methodology currently exists. The second goal of this research program is the elaboration of the chiral tertiary-carbinyl heterocyclic amine toward the total synthesis of kapakahine A and kapakahine F. The third goal of this research program is the preparation of different analogues and intermediates for biological evaluation in our open collaboration with the Nakao group at the University of Tokyo. PUBLIC HEALTH RELEVANCE Due to the increasing drug resistance of malaria and its migration into new areas of the world, new and innovative therapeutic remedies continuously need to be investigated. Although nature continues to supply mankind with compounds that exhibit promising anti-malarial activity, synthesis of these natural products is generally required to produce the quantity of material needed for biological evaluation. [unreadable] [unreadable] [unreadable]